Bone marrow will be processed via a new technology which will enrich hematopoietic stem cells and graft facilitating cells. Monitoring for chimerism will be done at key time points.

Detailed Description:

The objective for the study is to establish chimerism following reduced intensity conditioning with no grade III/IV GVHD. The primary endpoint we will follow is production of the missing enzyme at ≥ 10% of the normal level at day 180 post-transplant in > 90% of patients.

Eligibility

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion criteria:

Patients must have a confirmed diagnosis of inherited metabolic disorder / inborn error of metabolism. Diagnosis should be confirmed by appropriate test(s) (enzyme and/or mutation analysis) before study entry. Patients must not be eligible for myeloablative chemotherapy as a preparative regimen for transplant due to age, co-morbidities or organ dysfunction.

Inborn errors of metabolism / Inherited Metabolic Disorders (IMD) eligible for this study include the following:

Hurler Syndrome (MPS I)

Hurler-Scheie Syndrome with early neurologic involvement and/or sensitization to ERT

Hunter Syndrome (MPS II)

Sanfilippo Syndrome (MPS III)

Krabbe Disease (Globoid Leukodystrophy)

Metachromatic Leukodystrophy (MLD)

Adrenoleukodystrophy (ALD and AMN)

Sandhoff Disease

Tay Sachs Disease

Pelizaeus Merzbacher (PMD)

Niemann-Pick Disease

Alpha-mannosidosis

Patients must have adequate function of other organ systems as measured by:

Creatinine less than or equal to 2.0 mg/dl and creatinine clearance ≥60 cc/min/1.73m2. Newborns must have a creatinine clearance ≥ 25 cc/min. For babies less than or equal to 3 months of age, the raw value on glomerular filtration rate (GFR) must be ≥ 1 cc/kg/min.

Pulmonary function tests (PFTs) demonstrating forced expiratory volume at one second (FEV1) of ≥50% of predicted for age. If child is too young or unable to perform PFTs, crying vital capacity result of >50% of normal value for age or resting pulse oximeter >92% on room air or clearance by pulmonologist will be required.

Patient must have a related donor (identical or mismatched for 1, 2 or 3 Human Leukocyte Antigen (HLA)-A, -B or -DR loci).

Patient, and parent, or legal guardian must have given written informed consent according to FDA guidelines.

Patients must have a minimum life expectancy of at least 6 months.

Female patients of childbearing potential cannot be pregnant or lactating/breast-feeding and must be either surgically sterile, postmenopausal (no menses for the previous 12 months), or must be practicing an effective method of birth control as determined by the investigator (e.g., oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy).

Subjects who are pregnant, as indicated by a positive serum human chorionic gonadotropin (HCG) test

Subjects whose only donor is pregnant at the time of intended transplant

Subjects of childbearing potential who are not practicing adequate contraception as defined by the investigator at the site

Jehovah's witnesses being unwilling to be transfused

Patients that have any comorbid condition which, in the view of the Principal Investigators, renders the patient at too high a risk from treatment complications and regimen related morbidity/mortality.

Lack of related donors

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01372228